An Open-Label Phase 2 Study of Surufatinib in Patients with Neuroendocrine Tumours in Europe

Phase 1

Conditions: euroendocrine Tumours
MedDRA version: 21.0Level: PTClassification code 10052399Term: Neuroendocrine tumourSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2020-006118-19-IT

Lead Sponsor: Hutchison MediPharma Limited

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 76

Inclusion Criteria

1. Has histologically or cytologically documented, locally advanced, or metastatic NET and has progressed on at least 1 prior line of therapy, but no more than 3 therapies:
a. Cohort A: NET of lung origin
b. Cohort B: NET of small bowel origin
c. Cohort C: NET of non-small bowel, non-pancreas, and non-lung origin
d. Cohort D (DDI substudy): NET of any origin
2. Has radiologic evidence of progressive tumour within 12 months of study enrolment
3. Is willing and able to provide informed consent
4. Is =18 years of age
5. Has measurable lesions according to RECIST Version 1.1
6. Has absolute neutrophil count of = 1.5×109/L, platelet count of = 100×109/L, and haemoglobin = 9 g/dL
7. Has serum total bilirubin <1.5 times the upper limit of normal (ULN)
8. Has proteinuria <2+ by urinalysis, or 24-hour urine collection =1 g of protein, or urine protein: urine-creatinine ratio =1.9
9. Has alanine aminotransferase (ALT), AST, or alkaline phosphatase levels = 2.5 times the ULN
a. Patients with known liver metastases may have ALT, AST, and ALP = 3× the ULN 10. Has serum creatinine <1.5 times ULN or creatinine clearance = 60 mL/min
11. International normalised ratio (INR) >1.5 or activated partial thromboplastin time (aPTT) >1.5×ULN
12. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
13. Female patients of childbearing potential and male patients with partners of childbearing potential agree to use a highly effective form(s) of contraception that results in a low failure rate (<1% per year) when used consistently and correctly, starting during the screening period, continuing throughout the entire study period, and for 90 days after taking the last dose of study drug. Such methods include oral hormonal contraception (combined estrogen/progestogen or progestogen only) or highly effective non-oral hormonal contraception (e.g., Depo-Provera and Implanon) associated with inhibition of ovulation together with a barrier method (e.g., diaphragm, always containing a spermicide), intrauterine device, intrauterine hormone-releasing system, bilateral tubal ligation, vasectomized partner, or sexual abstinence in line with the preferred and usual lifestyle of the subject. Oral and non-oral hormonal contraception should always be combined with an additional contraceptive method (i.e., barrier method) because of a potential interaction with the study drug. The same criteria are applicable to male patients involved in this clinical study if they have a partner of childbirth potential, and male patients must always use a condom.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 38
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 38

Exclusion Criteria

1. Has an AE due to previous anti-tumour therapy that has not recovered to =CTCAE Grade 1, except alopecia and peripheral neurotoxicity with = CTCAE Grade 2 caused by platinum chemotherapy
2. Major surgery within previous 4 weeks or radiation therapy within 2 weeks prior to the start of treatment. Prior palliative radiotherapy for metastatic lesions is permitted if there is at least one measurable lesion that has not been irradiated.
3. Prior VEGF/VEGFR-targeted therapy
4. Has uncontrollable hypertension, defined as systolic blood pressure =140 mmHg and/or diastolic blood pressure =90 mmHg, despite antihypertensive medication
5. PT/INR >1.5 or activated partial thromboplastin time (aPTT) >1.5×ULN. For patients on Coumadin or coumadin-like products, please refer to Section 7.3.3)
6. Has gastrointestinal disease or condition within 6 months prior to first dose that investigators suspect may affect drug absorption, including, but not limited to, active gastric and duodenal ulcers, ulcerative colitis and other digestive disease, gastrointestinal tumour with active bleeding, or other gastrointestinal conditions that
could, in the investigators judgment, result in bleeding or perforation
7. Has a history or presence of a serious haemorrhage (>30 mL within 3 months) or haemoptysis (>5 mL blood within 4 weeks) within 6 months of first dose of study drug
8. Has clinically significant cardiovascular disease, including, but not limited to, acute myocardial infarction within 6 months prior to enrolment, severe/unstable angina pectoris or coronary artery bypass grafting, congestive heart failure =2 according to the New York Heart Association classification, ventricular arrhythmia that needs drug treatment, and left ventricular ejection fraction (LVEF) <50%
9. Has a mean corrected QT interval by Fridericia (QTcF) =480 ms
10. Has brain metastases and/or spinal cord compression untreated with surgery and/or radiotherapy, and without clinical imaging evidence of stable disease (SD) for 14 days or longer; patients requiring steroids within 4 weeks prior to start of study treatment will be excluded
11. Has a high risk of bleeding at screening due to tumour invasion into major vessels, such as pulmonary artery, the superior vena cava, or the inferior vena cava, as determined by investigators
12. Has arterial thrombosis or deep venous thrombosis within 6 months prior to first dosing, or thromboembolic events (including stroke and/or transient ischaemic attack) within 6 months prior to first dose of study drug
13. Use of strong inducers or inhibitors of CYP3A4 within 2 weeks before the first dose of surufatinib
14. For Cohort D, use of medications that are known substrates, inhibitors, or inducers of CYP3A or substrates of P-gp or BCRP within 3 weeks before the first dose of the drug cocktail
15. Prior history of other cancer except those treated with curative intent for in situ non-melanoma skin cancer, breast, or cervical cancer, or those treated with curative intent and no evidence of disease in the last 5 years prior to enrolment in the study
16. Has a clinically meaningful ongoing infection
17. Has clinical symptoms consistent with pancreatitis
18. Has a history of allergies to any ingredient of surufatinib or its capsule shell,
including tartrazine (E 102)

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the anti-tumour activity of surufatinib in patients with low-to intermediate-grade (Grade 1 or Grade 2), well differentiated NET;Secondary Objective: - To characterise the PK of surufatinib in patients with NET<br>- To evaluate the effect of surufatinib on cardiac repolarisation, as detected by<br>changes in ECG QTc, and the potential relationship with surufatinib plasma<br>concentrations<br>- To further characterise the antitumour activity of surufatinib in patients with NET<br>- Cohort D only: To evaluate the effects of repeat dosing of surufatinib on the<br>single-dose PK of CYP3A4, P-gp, and BCRP) substrates in patients with NET<br>- To evaluate the safety and tolerability of surufatinib in patients with NET;Primary end point(s): Disease Control Rate (DCR);Timepoint(s) of evaluation of this end point: 6 months

Secondary Outcome Measures

Name	Time	Method

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